Abstract

OBJECTIVE: Serum IgG4 concentrations are used to evaluate a diagnosis of IgG4- related disease (IgG4-RD), but the positive predictive value (PPV) of a very high IgG4 level is uncertain. This study evaluated the PPV of a very high IgG4 concentration for diagnosing IgG4-RD.METHODS: The data warehouses of two large academic healthcare systems were queried for IgG4 concentration test results. Cases with serum IgG4 concentrations >5x upper limit of normal (ULN) were included. Cases of IgG4-RD were determined using the ACR/EULAR Classification Criteria. The PPV for IgG4-RD of an IgG4 concentration >5x was estimated. Other conditions associated with very high IgG4 concentrations and specific features of IgG4-RD cases were characterized.RESULTS: IgG4 concentrations were available in 32,206 cases. Of these, 3,039 (9.4%) had elevated IgG4 concentrations, and a final cohort of 191 (0.6%) cases had IgG4 concentrations >5x ULN (median age 66 years, 72% male). The PPV of an IgG4 concentration >5x ULN for a diagnosis of IgG4-RD was 75.4% (95% CI 68.7-81.3). In the remaining cases, elevated IgG4 concentrations were observed among patients with malignancies, autoimmune diseases, and infections.CONCLUSION: The majority of cases with serum IgG4 concentrations >5x ULN in this study had IgG4-RD. These data support the high weight placed on very high serum IgG4 concentrations in the ACR/EULAR Classification Criteria. However, 25% of cases with very high IgG4 concentrations had an alternative diagnosis, underscoring the importance of considering the broad differential of etiologies associated with an elevated IgG4 concentration when evaluating a patient.

View details for DOI 10.3899/jrheum.220423

View details for PubMedID 36319016